This proposal is for the 9th to 13th years of the Simulation Resource Facility for Circulatory Mass Transport and Exchange at the University of Washington. Investigators from Michigan State University, University of Wisconsin, McGill, Duke University, Mayo Clinic, and the Netherlands collaborate in model development or analysis of experimental studies. The modeling analysis efforts of about 30 investigators focus on the kinetics of blood-tissue exchanges in well-perfused organs such as the normal heart, lung, and brain, and on approaches to assessment of both physiologic and pathophysiologic states such as ischemia, injury, and abnormalities of function and metabolism. Particular emphasis is on development and application of methods of interpreting data from positron emission tomography (PET) and from multiple tracer indicator dilution studies. The proposed program has three sections. Section I concerns development of analysis techniques for investigator-managed simulation analysis tools such as SIMCON and SCoP and development of a new simulation analysis system, SIMSYS, for enhanced optimization procedures accounting for constraints on parameter estimates and for the influences of noise in the data, and improved graphics tools. Section II, with 15 projects, is on model development in 5 categories: intercellular reactions, membrane transporters, capillary-tissue exchange units, whole organ heterogeneity (including fractal analysis) and a primitive recirculation model. Section III describes 13 projects for which no funding is requested. They apply the technology and models to the analysis of experimental and clinical data from PET imaging of the normal and abnormal heart, lung, brain, and tumors, with the emphasis on regional flows permeabilities, and metabolism of substrates for growth and energy metabolism and growth. These exemplify how the Facility's approaches and specific subroutine codes are being used. Three Cores are the computational facility itself, the code documentation and archiving, and dissemination of the scientific technology by symposia, workshops, and local training. There are internal and external advisory committees. The Resource's approaches are having impact in physiologic and radiologic disciplines.